#216 – Vincent Racaniello: Viruses And Vaccines | Lex Fridman Podcast

Key Takeaways

  • Viruses can diversify to infect anything because they can break into cells and steal proteins
  • The most lethal virus is actually rabies which will kill you if you get it; fortunately, it’s slow to develop and also the only virus that can be treated after exposure (bite)
  • SARS-CoV-2 is different than SARS-CoV-1 because shedding and transmission occurs before symptoms develop
  • The mRNA vaccine mechanism: RNA is put into lipid capsule for protection and injected into muscle then taken up into the cell
  • Vaccine hesitancy exists for a variety of reasons – the truth is we don’t know anything with 100% certainty so you have to weigh the effects of vaccine versus the effects of virus
  • Antiviral treatments must be administered quickly after the first sign and positive test – by the time you are in the hospital, it’s too late to work
  • It’s shocking that we have not put money into widespread, regular antigen testing at home
  • We need to stay vigilant to prepare for future pandemics – we have all the information to do what we need (study masks, antivirals, vaccines) – but we have short memories


Vincent Racaniello (@profvrr)  is a virologist, immunologist, and microbiologist at Columbia. He is a co-author of the textbook Principles of Virology and co-host of This Week in Virology podcast. To learn more about virology, check out his YouTube channel, MicrobeTV.

In this episode of the Lex Fridman Podcast, Lex and guest Vincent Racaniello review the origins and definition of a virus, break down the differences between influenza and coronaviruses, and take a deep dive into SARS-CoV-2 and COVID-19 – from vaccination hesitancy, antivirals, transmissibility, and much more!

Host: Lex Fridman (@lexfridman)

Understanding The Origins Of Viruses

  • There are more viruses in one liter of coastal seawater than there are people on earth!
  • There are orders of magnitude more bacterial viruses in the ocean alone than people in the world
  • Viruses have life cycles of minutes to weeks
  • Viruses were likely the first organic molecules to appear on earth
  • Reverse transcriptase is probably the earliest enzyme that arose to copy RNA to DNA and gave rise to the ability to build big cells
  • Bacteria are mostly single-cell organisms and don’t have the energy to become larger
  • Lifecycle: pre-cellular stage – self-replication molecules – cells arise – self-replicating molecules invade the cells – replicate in the cell and steal proteins to build a shell – released as virus particles, moving from host to host
  • Viruses can diversify to infect anything because they can break into cells and steal proteins
  • Hosts take longer to change & adapt than viruses
  • Viruses can be good and bad: we’re full of viruses that don’t hurt us and can even help us – most viruses we don’t worry about because they can’t infect us
  • We should worry most about viruses from bats, rodents, and birds
  • To learn more, check out Racaniello’s lecture “What is a virus?”

What Is A Virus?

  • A virus is a parasite – it takes from the host
  • There is usually not a symbiotic relationship between parasites and hosts
  • A virus cannot do anything without being inside a cell to take energy and replicate
  • Categories of viruses: RNA (older, faster evolution), DNA (slow, conservative)
  • Most everything on the planet is DNA based except viruses  
  • Unlike DNA, we don’t know how to manipulate RNA – you have to make a DNA copy of any RNA virus, modify it, and then put it back into cells
  • RNA viruses are more infectious, faster to evolve, and can infect any host – even just one genome might be right for infecting a person if it ever encounters someone
  • RNA viruses operate at the threshold of error: the measurement of genetic information that must be maintained to ensure survival; even one additional mutation will kill the virus
  • Most viruses have attachment mechanisms, except for viruses of yeast and fungi
  • A virus-infected cell is alive but the particle itself would not do anything without a cell
  • We often see deadly viruses that are not highly transmissible (Ebola, rabies) – and less deadly viruses that are highly transmissible but rarely highly transmissible and highly deadly
    • Viruses want to replicate and spread but if they killed you too fast, that wouldn’t happen
  • “I think viruses have strong selection pressure against being lethal and for being more transmissible” – Vincent Racaniello
  • Viruses really started spreading more rapidly as humans lived more densely in cities

What Can Kill Us?

  • “The things that can kill you are a minority of everything that’s out there.” – Vincent Racaniello
  • We have proteins that can kill us within our bodies if they misfold and replicate that way
  • Viruses and bacteria can cause infection in us – most we know how to treat
  • Some viruses have been shown to change host behavior in order to spread
  • Fungi can multiply at a microscopic level, and we can inhale spores if immunosuppressed
  • Parasites can invade humans and cause various levels of disruption
  • We usually acquire parasites through food: toxoplasmosis is most concerning for pregnant women who can give birth to deformed infants, but it comes from raw food
  • Be careful about food and water when traveling, particularly when going overseas
  • The most careful way to avoid parasites when traveling is to only eat cooked foods (e.g., no salad, no raw fruits, no sushi, etc.) – but we can treat most parasites
  • The most lethal virus is rabies: rabies will kill you if unvaccinated – but the rabies vaccine is the only vaccine that’s therapeutic (can be given after exposure because the disease takes time to develop)
  • We do immunize wild animals for rabies to reduce the incidence of rabies in the wild


  • SARS-CoV-2 is the virus, COVID-19 is the disease
  • “This is probably a once in a hundred years pandemic” – Vincent Racaniello
  • SARS-CoV-1 versus SARS-COV-2:
    • SARS-CoV-1: the peak of shedding (spreading virus) happened after patients were already in the hospital – there was not much pre-symptomatic or asymptomatic shedding
    • SARS-CoV-2: shedding and transmission before symptoms develop (if symptoms ever develop)
  • We should’ve had antivirals ready for coronaviruses after SARS-CoV-1 but stopped studies & research because that immediate concern was gone
  • SARS-CoV-2 is a coronavirus with spike proteins in membranes to attach to cells and are viruses with the longest known RNAs
  • SARS-CoV-2 genome is different from SARS-CoV-1 even though both bind to ACE1
  • You can use animal models to look at shedding and transmission of the virus, but no animals have died from COVID-19 so information is limited
  • SARS-CoV-2 is extremely long so more difficult to do basic experiments on the virus
  • Building a vaccine or antiviral drug requires you to figure out how to attack various targets and structural parts of the virus (usually target is an enzyme)

Families Of Viruses: Coronavirus Versus Influenza

  • General similarities: membranes, spike proteins (but different spikes),
  • Viruses with RNA can have three different types of RNA – plus, minus, plus/minus
    • Plus: ribosomes latch on to plus RNA to make protein
    • Negative: has to copy first or it won’t make proteins
    • Plus/minus: a combination of plus and minus
  • Main differences: coronaviruses are RNA+ (starts infectious cycle right away) while influenzas are RNA- (can’t be translated once they get into the cell), influenza is segmented while coronaviruses are in one piece
  • Influenza viruses vary widely in lethality
  • “We will never exterminate influenzas because every shorebird in the world is infected with them.”– Vincent Racaniello

Types Of Vaccines

  • The general goal of a vaccine is to deploy something in the body that is close to an actual virus but doesn’t have the same harmful effects
  • Egg-replicated: grow the virus in egg then inject
  • Replication competent: virus reproduces in you; select for mutations that don’t cause disease but illicit immune response (e.g., polio, measles, mumps, rubella)
  • Vector vaccine: use viruses that won’t make you sick (e.g., adenovirus) to deliver proteins of virus you want to prevent
  • mRNA: protect RNA in lipid capsule and inject – lipid nanoparticles get injected into the muscle and taken up into the cell
  • Low efficacy of flu vaccines: flu vaccines are based on inactivated virus vaccines which aren’t very close to actual influenza and reduce the efficacy
  • Sign versus symptom:
    • Symptom: perception, lived experience of what you feel – i.e., sore throat, stomachache
    • Sign: what can be measured to tell you more about infection
  • Polio vaccine was a letdown because so many kids got paralyzed as a side effect – it wasn’t properly inactivated

Discussing Vaccine Hesitancy

  • Many people are afraid because mRNA is a relatively new technology
  • There’s a natural distrust of the government enforcing vaccines – there’s an individualist spirit to Americans resisting overreach of government
  • A major concern seems to be less about long-term effects and more about the misrepresentation of data which has created mistrust – and leads to conspiracies and a sense of ‘what are they hiding?’
  • Clinical trials data is public: should be trusted because once you start fabricating data at this scale, inconsistencies would be easy to pick up
  • It makes sense that our for-profit medical system will come with hesitancy
  • It’s strange we don’t seem to have the same concern about pharmaceuticals as we do about vaccines and antivirals
  • The good thing about mRNA is it doesn’t last forever and certainly not as long as DNA
  • Proteins made after RNA gets into cell also have a finite lifespan of a few weeks at best
  • It’s injected deep into the deltoid muscle so it doesn’t go into blood vessels for widespread circulation
    • Spread in mice only happened at 1000x dose given
  • mRNA codes for the spike: the one thing we know about spike protein is it can cause fusion of cells but the spike in the vaccine has been modified to avoid fusion
  • The best test of vaccine is putting it in people – most effects of vaccine you will see within a couple of months
  • The truth is we don’t know anything with 100% certainty: you have to weigh the effects of vaccine versus the effects of the virus
  • It’s one thing to have concerns about the vaccines, it’s another thing to put out misinformation and things that are flat out untrue
  • Maybe the way forward should have been/should be – here’s the vaccine, it’s available to those who want it, and let’s move on

Will Vaccines Enable Creation Of Stronger Strain Of COVID?

  • Remember, viruses are always mutating
  • Natural infection and vaccination select for variance by inducing immunity
  • Mutations at the core of variants were always there – vaccine or natural infection did not create them
  • Any single mutation, even just one genome might be right for infecting a person if it ever encounters that person
  • We can create a vaccine that protects against all variants
  • People who have had natural immunity (been infected with SARS-CoV-2) plus one dose of the vaccine have a more robust immune response against all strains versus those who have both doses of vaccine
  • It’s worth investigating whether we should be mixing and matching the vaccines instead of getting all doses from one brand

Antivirals For COVID-19

  • Discussions of ivermectin were censored from YouTube
  • Ivermectin is FDA approved off-label and is safe at the approved levels
  • Current COVID treatment in some places: a combination of remdesivir, dexamethasone, ivermectin
  • It’s possible that more money was put into vaccines versus pharmaceuticals because vaccines offer long-term relief versus pharmaceuticals which protect at the moment
  • Hydroxychloroquine is an anti-malarial that blocks infection with a lot of viruses – but it has no effect on the lung because  the virus can bypass it
  • Hydroxychloroquine scientifically could not work for COVID but it’s possible that the narrative around hydroxychloroquine drove the conspiracy feelings around ivermectin
  • By the time you are in the hospital with COVID, you probably can’t breathe and the problem is now inflammatory – no antiviral will help because it’s used late
  • You need a pill shortly after your first positive test quickly after your first sore throat – it’s too late by the time you get to the hospital
  • We have to reduce the resurgence of resistance by having a cocktail of antivirals available

Ins And Outs Of COVID-19 Testing

  • Polymerase chain reaction (PCR) tests: measures viral RNA load, diagnostic which measures whether you have bits of RNA in you to test infection
  • In the early days, no matter what level of cycle threshold you had you would be quarantined which was incorrect because you aren’t shedding at every level
  • Antigen tests: look for proteins that the virus is making
  • Antigen tests would have been perfect for daily testing – though they have more errors but you could test more frequently to get the picture of what’s going on
  • Antigen testing would still be valuable to widely manufacture and distribute to prevent transmission
  • In future pandemics, we need a rapid antigen test right off the bat
  • Most people don’t have an objection to testing – it would be a great solution
  • There’s economic pressure against testing because they’re so cheap and won’t make a lot of money – we also have vaccines so testing will be a tougher sell

Masks & Transmissibility of COVID-19

  • COVID-19 is transmitted through the air – when you talk, you expel droplets with virus
  • Big droplets fall to the ground, little droplets can go far but probably don’t have enough virus to infect
  • “80% of transmissions are done by 20% of infected people” – Vincent Racaniello
  • You can’t replicate droplet transmission in real life, so we use epidemiology which makes it harder to develop solutions
  • Some epidemiological experiments have been done with virus-free droplets and masks, so mask-wearing is largely based on models
  • We lack a good understanding of how well masks work which has led to the politicization of mask-wearing all together
  • There’s a division that’s been created in mask-wearing because the narrative has been so bad – flip-flopping by WHO and CDC, lack of clarity in types of masks, etc.

COVID-19 In Kids

  • It’s possible the larger narrative in increasing vaccines is to protect kids who have no say in the matter of what’s happening – [are kids an excuse for control, this wouldn’t be the first time – Podcast Notes]
  • [Masking kids has been shown to be ineffective, but is still mandated for children as young as 2 – The USA is the only country requiring this and without any legitimate scientific support and to the clear detriment of children – Podcast Notes]
  • If children get infected, they will get less sick but it’s not zero consequences
  • It’s arguable there should be an effort to increase vaccinations as kids go back to school to protect the children since they have no say in what’s happening
  • The reality is we don’t know about the long-term effects of the vaccine or long COVID in kids

Critiques Of Dr. Fauci & Balancing COVID

  • Communication to the public was flubbed
  • Fauci lacks authenticity and seems like he’s not speaking to the fullest truth and with authority
  • The reality is no one is an authority on this new virus
  • There should’ve been more openness about the origins of the virus
  • Fauci is uneasy going against the mainstream ideas or even having tough conversations, owning up to mistakes, acknowledging what we don’t know, etc.
  • There are atrocities all around the world – we care about COVID right now because that’s where the attention is – are we overreacting?
  • There’s a significant increase in distrust of science
  • Even if some of the mishandling is not Fauci’s fault, there has to be a leader that falls on the sword

Alternative solutions weren’t being explored in a timely way: We should’ve had widespread testing in 2020, we should’ve explored antivirals and been open to off-label use, the true efficacy of mask-wearing, and what type of mask should have been studied

Lex Fridman Podcast : , , , ,
Notes By Maryann

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